P23: UFO: Utility-Based Curve-Free Phase I/II Clinical Trial Design Identifying the Optimal Dose of Immunotherapies

Conference: ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2023
09/29/2023: 9:45 AM - 10:30 AM EDT
Posters 
Room: White Flint Foyer 

Description

Immunotherapy is a cutting-edge treatment that utilizes the patient's immune system to combat cancer. However, current clinical trial designs for immunotherapy rely on intricate parametric models that are challenging to validate in practice and interpret clinically, hindering the translation of statistical design into practical trial implementation and producing undesirable outcomes. To address these issues, we propose the UFO design, a curve-free phase I/II clinical trial design that incorporates the distinct characteristics of immunotherapy to identify the optimal biological dose (OBD) that maximizes the risk-benefit trade-off for patients. The UFO design dynamically determines the dose escalation and de-escalation by simultaneously considering immune response, toxicity, and efficacy, allocating patients to the dose with the highest desirability in the risk-benefit tradeoff. Unlike most existing designs, the UFO design does not rely on any parametric model assumptions and produces favorable results under any clinically significant dose-response curves. Additionally, we have extended the UFO design to handle delayed outcomes. Our comprehensive simulation studies demonstrate that the UFO design produces favorable operating characteristics.

Keywords

Phase I/II clinical trials

Immune response

Immunotherapy

Risk–benefit tradeoff

Delayed outcomes 

Presenting Author

Yingjie Qiu, Indiana University

CoAuthor(s)

Yong Zang, Indiana University
Yi Zhao, Indiana University

Topic Description

Clinical Trial Design (e.g., Innovative/Complex Design, Estimands, Master Protocol)
ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2023